Proleukin

Proleukin 18 million IU powder for solution for injection or infusion

Aldesleukin

Read all of this leaflet carefully before you are given this medicine.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

• 1. What Proleukin is and what it is used for


• 2. Before you are given Proleukin


• 3. How Proleukin is used


• 4. Possible side effects


• 5. How to store Proleukin


• 6. Further information

What Proleukin Is And What It Is Used For

Proleukin is the brand name of aldesleukin. It is a synthetic protein, very similar to a protein produced by the body called interleukin-2 (IL-2). This protein is part of the immune system. IL-2 activates certain white blood cells in the body called lymphocytes, which fight against diseases and infections. IL-2 stimulates the production of lymphocytes in the body, and enhances the body's defences.

Proleukin is used to treat kidney cancer which has spread to other organs (also called metastatic renal cell carcinoma).

Before You Are Given Proleukin

Follow carefully all instructions given to you by your doctor.

Your doctor may carry out tests before you are treated with Proleukin. He/she will check your response to the treatment at regular intervals and take any necessary action.

You should not be given Proleukin

• If you are allergic (hypersensitive) to adesleukin or any of the other ingredients of Proleukin.



• If you are confined to bed for more than half the day.



• If it is less than 24 months since your kidney cancer was diagnosed and you have cancer symptoms, even if the cancer has spread to other organs.



• If you have a history of heart disease.



• If you have an infection for which you are taking antibiotics.



• If you have a shortage of oxygen in your blood.



• If you have serious problems with your liver, kidneys or any other organs.



• If you suffer from seizures (convulsions or fits), or from brain cancer that has not been successfully treated.



• If you have had an organ transplant.



• If you currently use medicines called corticosteroids to treat inflammatory reactions or if you may require these during Proleukin therapy.



• If you have had rheumatoid arthritis, Crohn's disease or any other disease caused by your own immune system.

If any of the above applies to you, talk to your doctor. You should not be given Proleukin.

Also, Proleukin should not be given to you if blood tests show that:

You have a low level of white blood cells, platelets or red blood cells.

You have creatinine or bilirubin levels outside the normal range.

Take special care with Proleukin

• If you have chest pain or irregular heart beat. In some patients an electrocardiogram (ECG) will be carried out at regular intervals.



• If you become short of breath or you start breathing faster during treatment.



• If you feel extremely tired or sleepy, because this may be a signal that you are losing consciousness.

If you get any of the symptoms listed above, tell your doctor immediately.

You should also take special care:

• If you have a fever, shivers, chills, nausea and/or diarrhoea.



• If you feel dizzy. This may be a sign that you have low blood pressure, often seen within 2 to 12 hours after starting Proleukin administration.



• If you have a bacterial infection, since Proleukin treatment puts you at a higher risk of infection.



• If you notice mood changes. These in general return to normal after stopping therapy.



• If you have diabetes. Your blood sugar levels may increase or decrease more than usual.



• If you have a very itchy red rash or if your skin gets extremely dry during the treatment with Proleukin.

If any of the symptoms listed above gets severe, tell your doctor.

Using other medicines

Some medicines can decrease the effect of Proleukin, or increase side effects.

Tell your doctor or pharmacist if you are using any of the following medicines (or have recently used them).

• Chemotherapy medicines, called tamoxifen, interferon-alpha, cisplatin, vinblastine and/or dacarbazine, used to treat cancer.



• Medicines called glucocorticoids (a type of steroid), used to treat inflammatory reactions.



• Medicines called beta-blockers, used to treat high blood pressure.



• Medicines that affect the heart, central nervous system, liver, kidneys or bone marrow. Consult your doctor if you are not sure what these are.



• Contrast fluids used in Computerised Tomography (CT) scanning.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Children and adolescents (below 18 years)

Proleukin is not recommended for children and adolescents younger than 18 years.

Older people (65 years and over)

Older patients may be more susceptible to the side effects of Proleukin. Medical staff should take extra care when treating older people.

Pregnancy and breast-feeding

• Tell your doctor before starting treatment if you are pregnant, if you suspect that you are pregnant, or if you intend to become pregnant. Your doctor will discuss with you the risks and benefits of taking Proleukin during pregnancy.


• Both male and female patients should use effective contraception while being treated with Proleukin in order to prevent pregnancy. This is done with most other medicines used to treat cancer.


• Stop breast-feeding during treatment with Proleukin as there is a possibility that serious side effects could affect the baby.

Ask your doctor or pharmacist for advice before taking any medicine, while you are pregnant or breast-feeding.

Driving and using machines

Do not drive or use any tools or machines because Proleukin has side effects which may influence your ability to carry out these activities.

How Proleukin Is Used

Proleukin can be given to you:

• either as a drip into a vein (intravenous infusion). This should be carried out in the hospital, under supervision of a doctor or nurse experienced in the use of medicines to treat cancer,


• or by injection directly under the skin (subcutaneous injection). This can be administered in a hospital, in an outpatient's department or at home, under supervision of a doctor or nurse.

Before and during your Proleukin therapy, your doctor may perform regular blood tests and chest X-rays, to check your organs and your blood cell counts.

Follow all instructions given to you by your doctor or nurse carefully.

If you have been given more Proleukin than you should

If you have or think you have been given too much Proleukin, contact your doctor or nurse immediately. You might get some of the side effects described in section 4.

Proleukin Side Effects

Like all medicines, Proleukin can cause side effects, although not everybody gets them. The side effects of Proleukin usually disappear within two days after stopping treatment.

Your doctor may consider it necessary to treat the side effects of Proleukin with other medicines.

Some side effects can be serious

Very common (affecting more than 1 in 10 patients) or common (affecting less than 1 in 10 patients):

• Blood disorders: low levels of white blood cells (leucopenia) with symptoms of fever or increased risk of infections; low levels of platelets in your blood with bruises and spontaneous bleeding (thrombocytopenia); low levels of red blood cells (anaemia) with symptoms such as fatigue and pale skin; blood clotting disorders with sudden onset of shortness of breath, bloody sputum, leg pain or easy bleeding.


• Heart and circulation problems: oppressive chest pain (angina); low blood pressure (hypotension) or high blood pressure (hypertension) associated with dizziness, blurred vision or constant headache; irregular heart beat (arrhythmia); fast heart beat (tachycardia); blue colour to the lips, tongue and skin due to oxygen deficiency in the blood (cyanosis).


• Breathing and lung problems: coughing; shortness of breath (dyspnoea) or chest discomfort.


• Kidney and urine problems: low urine production (oliguria), with high levels of urea and creatinine in the blood with symptoms such as vomiting, sleepiness, poor muscle tone or difficult breathing; blood in the urine (haematuria).


• Digestive and organ problems: stomach, intestine and rectal bleeding (resulting in black stools); vomiting blood (haematemesis); swelling of the belly (ascites); difficulty in swallowing (dysphagia).


• Nerve problems: sudden unconsciousness or fainting (syncope); loss of ability to speak.


• Feeling cold due to low body temperature (hypothermia); low level of calcium (hypocalcaemia) with possible muscle weakness, twitching or tingling of fingers; high level of potassium (hyperkalaemia) associated with cramps, abnormal heart rhythm, dizziness and headache.

If you experience any of the effects listed above, contact your doctor immediately or go to the nearest emergency unit.

Uncommon (affecting less than 1 in 100 patients) or rare (affecting less than 1 in 1,000 patients):

• Blood disorders: low levels of white blood cells with signs and symptoms of sudden high fever, severe sore throat, and more frequent infections (agranulocytosis); formation of blood clot (thrombosis); bleeding (haemorrhage).


• Heart problems: heart attack (myocardial infarction, myocardial ischemia); disorders of heart and blood vessels, such as abnormal or insufficient pumping force of the heart (heart failure); irregular heart beat; disease of the heart muscle with symptoms such as chest pain, fever or malaise; awareness of an abnormal heart beat (palpitations).


• Lung problems: sudden onset of breathing difficulty due to blood clots in the lung (pulmonary embolism); extreme difficulty in breathing (adult respiratory distress syndrome); coughing up blood (haemoptysis).


• Serious allergic reactions: anaphylaxis, leading to swelling of the face and throat and difficulty breathing (Quincke's oedema); high fever, skin rash with small blisters, joint pain and/or eye inflammation (Stevens Johnson syndrome.


• Digestive and organ problems: recurring (severe) inflammation of the bowels (Crohn's disease) accompanied with diarrhoea, pain in lower abdomen, fever, and weight loss; inflammation of the pancreas (pancreatitis) accompanied with severe pain in upper abdomen radiating to the back; constipation, swollen abdomen, abdominal pain (intestinal obstruction); upper abdominal pain (cholecystitis); liver failure with abdominal pain, fatigue, yellowish skin and eyes or dark yellow urine.


• Kidney failure associated with fatigue, sleepiness, loss of appetite, vomiting or swollen legs.


• Nerve problems: seizures (convulsions or fits); paralysis; coma; disturbances of the sight (optic neuropathy); central nervous lesion with tingling, numbness (paraesthesia) or loss of control of movement.


• Decreased or increased thyroid activity (hypo- or hyperthyroidism) with symptoms such as weight gain, weight loss, sweating or hearing loss; low glucose level (hypoglycaemia) associated with symptoms such as feeling hungry, sweating, dizziness, heart palpitations; high blood calcium level (hypercalcaemia) with symptoms such as feeling sick (nausea), vomiting or constipation.

If you experience any of the effects listed above, contact your doctor immediately or go to the nearest emergency unit.

Other side effects

Very common (affecting more than 1 in every 10 patients):

• Loss of appetite (anorexia).


• Anxiety; confusion; dizziness; headache; drowsiness (somnolence).


• Cough.


• Feeling sick (nausea) with or without vomiting; diarrhoea; mouth sores with inflammation (stomatitis).


• Redness of the skin (erythema), skin rash; peeling; itching.


• Reactions at injection site, such as pain and inflammation.


• Flu-like symptoms (fever, chills, malaise, fatigue); pain; weight loss, weight gain.

If any of these gets severe, tell your doctor or pharmacist.

Common (affecting less than 1 in 10 patients):

• Nose, throat and pulmonary infections; stuffed nose (nasal congestion).


• Dehydration with signs such as dryness of the mouth or feeling thirsty.


• Mood changes, e.g. irritability, excitement and restlessness (agitation), depression, observation of things which are not there (hallucinations); difficulty in sleeping (insomnia).


• Loss of control of movements, observation of itching and tingling of fingers or toes without cause (paraesthesia, neuropathy).


• Stomach discomfort after meal (dyspepsia); constipation.


• Sweating; loss of hair (alopecia).


• Muscle pain; joint pain.


• Eye inflammations (conjunctivitis) with itching redness and swelling.


• Swelling and reddening of a vein (phlebitis).


• Fluid accumulation (oedema); inflammation of mucous membranes (mucositis); swelling with nodes (nodules) at site of injection.


• High level of blood glucose (hyperglycaemia) with signs such as excessive thirst, hunger, urination or fatigue.


• Blood tests indicating a change in liver function e.g. high level of bilirubin (hyperbilirubinaemia) or liver enzymes in the blood (liver transaminase, alkaline phosphatase and lactate dehydrogenase).

If any of these gets severe, tell your doctor or pharmacist.

Uncommon (affecting less than 1 in 100 patients):

• Allergy reactions (hypersensitivity) leading to runny eyes, runny nose, skin rash or distress.


• Muscle weakness (myasthenia)


• Loss of taste.


• Nose bleeding (epistaxis).


• Inflammation of the lips (cheilitis); inflammation of the stomach resulting in stomach ache and nausea (gastritis).


• Skin discolouration (vitiligo).

If any of these gets severe, tell your doctor or pharmacist.

Rare (affecting less than 1 in 1,000 patients):

• Diabetes.


• Lethargy with signs of luck of energy, tiredness and sleepiness.


• Skin rash with small blisters filled with fluid (vesiculobullous rash).


• Tissue damage (necrosis) at injection site.

If any of these gets severe, tell your doctor or pharmacist.

Inflammation of the blood vessels (vasculitis) in the skin, brain, and rest of the body, has also been reported.

If any of the side effects gets severe, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Proleukin

Keep out of reach and sight of children.

Do not use Proleukin after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.

Store the unopened vials in a refrigerator (2°C-8°C). Do not freeze.

Store in the original package.

Your doctor, nurse or pharmacist knows how to store Proleukin properly.

Further Information

What Proleukin contains

• The active substance is aldesleukin, providing 18 million International Units (IU) (1.1 mg) per millilitre of solution reconstituted as recommended.


• The other ingredients are mannitol (E421), sodium laurylsulfate, sodium dihydrogen phosphate and disodium hydrogen phosphate.

What Proleukin looks like and contents of the pack

Proleukin is a sterile, white powder available in packs containing 1 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Pharmaceuticals UK Ltd

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

Manufacturer

Novartis Pharmaceuticals UK Ltd

Wimblehurst Road

Horsham West Sussex

RH12 5AB

UK

This leaflet was last approved in August 2008.